Biology subjects

Liu, C. J.

Publications and source records attributed to Liu, C. J..

13 recordsLinked to original sources

bioRxiv2026

Enhancing precision medicine for patients with breast cancer brain metastases through functional drug testing

Patient-derived organoids from breast cancer brain metastases enable real-time drug sensitivity testing integrated with genomic profiling. Drug response varied by subtype and molecular alterations. PI3K inhibitors showed activity regardless of PIK3CA mutation status. Pronounced tumor heterogeneity highlighted the urgent need for effective therapies personalized for each patient. Functional assays and molecular matching can help tailor therapy for patients who need the most effective next treatment quickly and warrant further translational evaluation to address this unmet need.

cancer biology↗

bioRxiv2025

AncestryHub: A web server for local ancestry analysis

SummaryAncestryHub is a web version of local ancestry analysis software. It contains four built-in software and a set of built-in population reference panels. AncestryHub will significantly reduce the efforts and requirements for the users on their personal computational skills and computational hardware environment for ancestry analysis. Availabilityhttps://www.ancestryhub.4dgenome.com Contact: lima@4dgenome.com

bioinformatics↗

bioRxiv2024

Primary auditory thalamus relays directly to cortical layer 1 interneurons

Inhibitory interneurons within cortical layer 1 (L1-INs) integrate inputs from diverse brain regions to modulate sensory processing and plasticity, but the sensory inputs that recruit these interneurons have not been identified. Here we used monosynaptic retrograde tracing and whole-cell electrophysiology to characterize the thalamic inputs onto two major subpopulations of L1-INs in the mouse auditory cortex. We find that the vast majority of auditory thalamic inputs to these L1-INs unexpectedly arise from the ventral subdivision of the medial geniculate body (MGBv), the tonotopically-organized primary auditory thalamus. Moreover, these interneurons receive robust functional monosynaptic MGBv inputs that are comparable to those recorded in the L4 excitatory pyramidal neurons. Our findings identify a direct pathway from the primary auditory thalamus to the L1-INs, suggesting that these interneurons are uniquely positioned to integrate thalamic inputs conveying precise sensory information with top-down inputs carrying information about brain states and learned associations.

neuroscience↗

bioRxiv2023

Behavioral control through the direct, focal silencing of neuronal activity

Voltage-gated sodium channel (NaV) activity underlies electrical signaling, synaptic release, circuit function, and, ultimately, behavior. Molecular tools that enable precise control of NaV subpopulations make possible temporal regulation of neuronal activity and cellular communication. To rapidly modulate NaV currents, we have rendered a potent NaV inhibitor, saxitoxin, transiently inert through chemical protection with a novel nitrobenzyl-derived photocleavable group. Light-induced uncaging of the photocaged toxin, STX-bpc, effects rapid inhibitor release and focal NaV block. We demonstrate the efficacy of this reagent for manipulating action potentials in mammalian neurons and brain slice and for altering locomotor behavior in larval zebrafish. Photo-uncaging of STX-bpc is a non-invasive, effective method for reversible, spatiotemporally precise tuning of NaV currents, application of which requires no genetic manipulation of the biological sample.

neuroscience↗

bioRxiv2022

Differential migration mechanics and immune responses of glioblastoma subtypes

Glioblastoma remains a deadly cancer driven in part by invasion of tumor cells into the brain. Transcriptomic analyses have identified distinct molecular subtypes, but mechanistic differences that account for clinical differences are not clear. Here, we show that, as predicted by the motor-clutch model of cell migration, mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their rapid migration and comparable proliferation rates in vitro, mice with mesenchymal tumors survive longer than those with proneural tumors. This improved survival correlated with an immune response in the mesenchymal tumors, including T cell-mediated. Consistently, inducing mesenchymal tumors in immunodeficient mice resulted in shorter survival supporting a protective immune role in mesenchymal tumors. Thus, mesenchymal tumors have aggressive migration, but are immunologically hot which suppresses net proliferation. These two features counteract each other and may explain the lack of a strong survival difference between subtypes clinically, while also opening up new opportunities for subtype-specific therapies. Significant StatementThis study highlights new mechanical and immunological insights into glioblastoma molecular subtypes using an integrated modeling-genome engineering strategy, which can potentially facilitate glioblastoma subtype-specific therapeutic strategies.

cancer biology↗

bioRxiv2021

Refractive-index matching enhanced polarization-sensitive optical coherence tomography quantification in human brain tissue

The importance of polarization-sensitive optical coherence tomography (PS-OCT) has been increasingly recognized in human brain imaging. Despite the recent progress of PS-OCT in revealing white matter architecture and orientation, quantification of fine-scale fiber tracts in the human brain cortex has been a challenging problem, due to a low birefringence in the gray matter. In this study, we investigated the effect of refractive index matching by 2,2-thiodiethanol (TDE) immersion on the improvement of PS-OCT measurements in ex vivo human brain tissue. We obtain the cortical fiber orientation maps in the gray matter, which reveals the radial fibers in the gyrus, the U-fibers along the sulcus, as well as distinct layers of fiber axes exhibiting laminar organization. Further analysis shows that index matching reduces the noise in axis orientation measurements by 56% and 39%, in white and gray matter, respectively. Index matching also enables precise measurements of apparent birefringence, which was underestimated in the white matter by 82% but overestimated in the gray matter by 16% prior to TDE immersion. Mathematical simulations show that the improvements are primarily attributed to the reduction in the tissue scattering coefficient, leading to an enhanced signal-to-noise ratio in deeper tissue regions, which could not be achieved by conventional noise reduction methods.

bioengineering↗

bioRxiv2021

The conventional dendritic cell 1 subset primes CD8+ T cells and traffics tumor antigen to drive anti-tumor immunity in the brain

The central nervous system (CNS) antigen presenting cell (APC) which primes anti-tumor CD8+ T cell responses remains undefined. Elsewhere, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain cDC1 are rare; cDC localize to choroid plexus and dura. Using preclinical glioblastoma models and cDC1-deficient mice, we explored the role of cDC1 in CNS anti-tumor immunity. We determined that cDC1 mediate checkpoint blockade-induced survival benefit and prime neoantigen-specific CD8+ T cells against brain tumors. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor-antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1-equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same subsets, we identified a tumor-specific fluorescent metabolite of 5- aminolevulinic acid, which labels tumor cells during fluorescence-guided glioblastoma resection. Together, these data elucidate the specialized behavior of cDC1 and suggest cDC1 play a significant role in CNS anti-tumor immunity. One Sentence SummaryCNS cDC1 engage in previously undefined behavior to establish immune responses against brain tumors.

immunology↗

bioRxiv2021

Ureterorenoscopic (URS) lithotripsy and balloon dilation cause acute kidney injury and distal renal tubule damage

Ureterorenoscopy (URS) is believed to be a safe and effective procedure to treat ureteral stone or ureteral stricture. Rapidly increased intrarenal pressure during URS may have a negative impact on the kidney, but the effect on renal functions is not well known. The aim of this study is to evaluate whether URS balloon dilation or lithotripsy would cause acute kidney injury (AKI), which was evaluated by urine neutrophil gelatinase associated lipocalin (NGAL) and renal tubular damage, which was evaluated by urine glutathione S-transferase (GST) and {pi}GST. This prospective study consisted of 207 patients with mean age 53.8 years old between September 2012 and June 2013. Four groups were included: the ureteral stricture group (group 1), the ureteral stone group (group 2), and two control groups. URS induced increased uNGAL on both Days 1 and 14 in both groups, and only elevated u-{pi}GST levels were noted on Day 14 after URSL. On Day 14, the difference between low-grade and high-grade hydronephrosis was significant in group 1 (p < 0.001) rather than group 2 (p = 0.150). By multivariate logistic regression analysis, age, baseline eGFR, and stone size > 1.0 cm were associated with complete recovery of hydronephrosis after URS on Day 14. Ureteral stone patients with preserved renal function suffered more AKI (uNGAL) than those with impaired renal function. However, URS-related AKI had no significant difference between stone [≤] 1 cm and > 1 cm subgroups. Besides, urine GST and {pi}GST were both significantly higher in stone > 1 cm subgroup when compared to [≤] 1 cm subgroup. In conclusion, URS laser lithotripsy and balloon dilatation all resulted in AKI and renal tubular damage on Day 14 though post-URS double-J (DBJ) stenting was performed in every patient.

biochemistry↗

bioRxiv2020

An Evolving-Dynamic Network Activity Approach toEpileptic Seizure Prediction using Machine Learning

Absence epilepsy is a neurological condition characterized by abnormally synchronous electrical activity within two mutually connected brain regions, the thalamus and cortex, that results in seizures and affects more than 6.5 million people. Epilepsy is commonly studied through the use of the electroencephalogram (EEG), a device that monitors brain waves over time. In this study, we introduced machine learning models to predict epileptic seizures in two ways, one to train logistic regression models to provide an accurate decision boundary to predict based off frequency features, and second to train convolutional neural networks to predict based off spectral power images from EEG. This pipeline employed a two model approach, using logistic regression and convolutional neural networks to predict seizures. The evaluation, performed on data from 9 mice, achieved prediction accuracies of 98%. The proposed methodology introduces a novel aspect of looking at predicting absence seizures, which are known to be short events, in addition to the comparison between a time-dependent and time-agnostic seizure prediction classifier. The overall goal of these experiments were to build a model that can accurately predict whether or not a seizure will occur.

neuroscience↗

bioRxiv2020

Improving laser standards for three-photon microscopy

SignificanceThree-photon excitation microscopy has double-to-triple the penetration depth in biological tissue over two-photon imaging and thus has the potential to revolutionize the visualization of biological processes in vivo. However, unlike the plug-and-play operation and performance of lasers used in two-photon imaging, three-photon microscopy presents new technological challenges that require a closer look at the fidelity of laser pulses. AimWe implemented state-of-the-art pulse measurements and developed new techniques for examining the performance of lasers used in three-photon microscopy. We then demonstrated how these techniques can be used to provide precise measurements of pulse shape, pulse energy and pulse-to-pulse intensity variability, all of which ultimately impact imaging. ApproachWe built inexpensive tools, e.g., a second harmonic generation frequency resolved optical gating (SHG-FROG) device, and a deep-memory diode imaging (DMDI) apparatus, to examine laser pulse fidelity. ResultsFirst, SHG-FROG revealed very large third order dispersion (TOD). This extent of phase distortion prevents the efficient temporal compression of laser pulses to their theoretical limit. Furthermore, TOD cannot be quantified when using a conventional method of obtaining the laser pulse duration, e.g., when using an autocorrelator. Finally, DMDI showed the effectiveness of detecting pulse-to-pulse intensity fluctuations on timescales relevant to three-photon imaging, which were otherwise not captured using conventional instruments and statistics. ConclusionsThe distortion of individual laser pulses caused by TOD poses significant challenges to three-photon imaging by preventing effective compression of laser pulses and decreasing the efficiency of nonlinear excitation. Moreover, an acceptably low pulse-to-pulse amplitude variability should not be assumed. Particularly for low repetition rate laser sources used in three-photon microscopy, pulse-to-pulse variability also degrades image quality. If three-photon imaging is to become mainstream, our diagnostics may be used by laser manufacturers to improve system design and by end-users to validate the performance of their current and future imaging systems.

bioengineering↗

bioRxiv2020

Three-photon imaging of synthetic dyes in deep layers of the neocortex

Multiphoton microscopy has emerged as the primary imaging tool for studying the structural and functional dynamics of neural circuits in brain tissue, which is highly scattering to light. Recently, three-photon microscopy has enabled high-resolution fluorescence imaging of neurons in deeper brain areas that lie beyond the reach of conventional two-photon microscopy, which is typically limited to ~450 m. Three-photon imaging of neuronal calcium signals, through the genetically-encoded calcium indicator GCaMP6, has been used to successfully record neuronal activity in deeper neocortical layers and parts of the hippocampus. Bulk-loading cells in deeper cortical layers with synthetic calcium indicators could provide an alternative strategy for labelling that obviates dependence on viral tropism and promoter penetration. Here we report a strategy for visualized injection of a calcium dye, Oregon Green BAPTA-1 AM (OGB-1 AM), at 500-600 m below the surface of the mouse visual cortex in vivo. We demonstrate successful OGB-1 AM loading of cells in cortical layers 5-6 and subsequent three-photon imaging of orientation- and direction-selective visual responses from these cells.

neuroscience↗

bioRxiv2019

CCLA: an accurate method and web server for cancer cell line authentication using gene expression profiles

Cancer cell lines (CCLs) as important model systems play critical roles in cancer researches. The misidentification and contamination of CCLs are serious problems, leading to unreliable results and waste of resources. Current methods for CCL authentication are mainly based on the CCL-specific genetic polymorphisms, whereas no method is available for CCL authentication using gene expression profiles. Here, we developed a novel method and homonymic web server (CCLA, Cancer Cell Line Authentication, http://bioinfo.life.hust.edu.cn/web/CCLA/) to authenticate 1,291 human CCLs of 28 tissues using gene expression profiles. CCLA curated CCL-specific gene signatures and employed machine learning methods to measure overall similarities and distances between the query sample and each reference CCL. CCLA showed an excellent speed advantage and high accuracy with a top 1 accuracy of 96.58% or 92.15% (top 3 accuracy of 100% or 95.11%) for microarray or RNA-Seq validation data (719 samples, 461 CCLs), respectively. To the best of our knowledge, CCLA is the first approach to authenticate CCLs based on gene expression. Users can freely and conveniently authenticate CCLs using gene expression profiles or NCBI GEO accession on CCLA website.

bioinformatics↗

bioRxiv2018

pVACtools: a computational toolkit to select and visualize cancer neoantigens

The elucidation of neoantigens is a critical step in predicting response to checkpoint blockade therapy and design of personalized cancer vaccines. We have developed an in silico sequence analysis method - pVACtools, to facilitate comprehensive neoantigen characterization. This modular workflow consists of tools for neoantigen prediction from somatic alterations (pVACseq and pVACfuse), prioritization and selection using a graphical web-based interface (pVACviz), and determining the optimal order of neoantigen candidates in a DNA vector-based vaccine(pVACvector).

bioinformatics↗